This proposal seeks to define the mechanisms of cochlear blood flow control. The proposal offers the hypothesis that the sensory neurons and Substance P (SP) are important factors contributing to vascular tone in the cochlea. The study has four specific aims. 1) Characterize the vasodilatation effect of capsaicin-sensitive primary sensory neurons on cochlear blood flow by applying capsaicin through the anterior inferior cerebellar artery (AICA) and the round window membrane (RWM). This will demonstrate the significant role of capsaicin fibers as part of the cochlear blood flow regulation system. 2) Measure capsaicin-induced changes in the permeability of cochlear blood vessels. The permeability change will be revealed by intravenous infusion of colloidal silver, followed by serial sectioning of the cochlea. This study will demonstrate a role of this neuropeptide system in cochlear fluid homeostasis. 3a) Characterize the effect of SP neurotransmitter on cochlear blood flow and 3b) pharmacologically block the SP-based, capsaicin-induced cochlear vasodilatation. This will provide direct evidence for a significance of contribution of SP in the regulation of cochlear blood flow. 4a) Measure changes in cochlear vasodilatation produced by the capsaicin-sensitive neurons and neuropeptides in the hydropic guinea pig. The animal model of hydrops is a significant type of homeostatic pathology in the cochlea. This aim will determine if hydrops also alters the neuropeptide vasodilatative mechanisms. 4b) Measure the cochlear blood flow (CBF) change after capsaicin application in diabetic rat. The non-invasive laser Doppler flowmetry method for measurement of cochlear blood flow will be used in these experiments.